Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Clonal hematopoiesis is driven by aberrant activation of TCL1A [CITE-seq]

ABSTRACT: We used single cell RNA sequencing (scRNA-seq) to analyze the different cell populations present after in vitro culture of HSPCs with or without TCL1A overexpression.

ORGANISM(S): Homo sapiens

PROVIDER: GSE205636 | GEO | 2022/12/20

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Clonal hematopoiesis is driven by aberrant activation of TCL1A [ATAC-seq]

Project description:We used OMNI-ATAC to analyze the chromatin accessibility of TCL1A in TET2 edited HSPCs.

2022-12-20 | GSE205635 | GEO

Clonal hematopoiesis is driven by aberrant activation of TCL1A [CITE-seq]

Project description:Clonal hematopoiesis is driven by aberrant activation of TCL1A [CITE-seq]

| PRJNA846749 | ENA

Clonal hematopoiesis is driven by aberrant activation of TCL1A

Project description:Clonal hematopoiesis is driven by aberrant activation of TCL1A

| PRJNA846748 | ENA

Clonal hematopoiesis is driven by aberrant activation of TCL1A [ATAC-seq]

Project description:Clonal hematopoiesis is driven by aberrant activation of TCL1A [ATAC-seq]

| PRJNA846750 | ENA

Clonal hematopoiesis is driven by aberrant activation of TCL1A

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-12-20 | GSE205637 | GEO

Aberrant Clonal Hematopoiesis following Lentiviral Vector Transduction of HSPCs in a Rhesus Macaque

Project description:Lentiviral vectors (LVs) are used for delivery of genes into hematopoietic stem and progenitor cells (HSPCs) in clinical trials worldwide. LVs, in contrast to retroviral vectors, are not associated with insertion site-associated malignant clonal expansions and, thus, are considered safer. Here, however, we present a case of markedly abnormal dysplastic clonal hematopoiesis affecting the erythroid, myeloid, and megakaryocytic lineages in a rhesus macaque transplanted with HSPCs that were transduced with a LV containing a strong retroviral murine stem cell virus (MSCV) constitutive promoter-enhancer in the LTR. Nine insertions were mapped in the abnormal clone, resulting in overexpression and aberrant splicing of several genes of interest, including the cytokine stem cell factor and the transcription factor PLAG1. This case represents the first clear link between lentiviral insertion-induced clonal expansion and a clinically abnormal transformed phenotype following transduction of normal primate or human HSPCs, which is concerning, and suggests that strong constitutive promoters should not be included in LVs.

2020-06-25 | GSE153130 | GEO

Aging-elevated inflammation promotes DNMT3A R878H-driven clonal hematopoiesis.

Project description:Aging-elevated DNMT3A R882H-driven clonal hematopoiesis (CH) is a risk factor for myeloid malignancies remission and overall survival. Although some studies were conducted to investigate this phenomenon, the exact mechanism is still under debate. In this study, we observed that DNMT3A R878H bone marrow cells (human allele: DNMT3A R882H) displayed enhanced reconstitution capacity in aged bone marrow milieu and upon inflammatory insult. DNMT3A R878H protects hematopoietic stem and progenitor cells from the damage induced by chronic inflammation, especially TNFα insults. Mechanistically, we identified that RIPK1-RIPK3-MLKL-mediated necroptosis signaling was compromised in R878H cells in response to proliferation stress and TNFα insults. Briefly, we elucidated the molecular mechanism driving DNMT3A R878H-based clonal hematopoiesis, which raises clinical value for treating DNMT3A R882H-driven clonal hematopoiesis and myeloid malignancies with aging.

| S-EPMC8897035 | biostudies-literature

Inflammatory signals from fatty bone marrow support DNMT3a-driven clonal hematopoiesis (wt/DNMT3A KI subset)

Project description:Accumulation of fatty bone marrow (FBM) is one of the key age related changes possibly influencing the blood system. While a link between obesity and cancer evolution has been reported it remains unknown whether FBM can modify the evolution of the early stages of leukemia and clonal hematopoiesis (CH). To address this question, we established different FBM mouse models in immunodeficient mice in whom we can study both mouse and human cells. We focused our studies on two FBM models: 1) after sublethal irradiation; 2) after castration; and in both we used an adipogenesis inhibitor as a control (PPARγ inhibitor). We transplanted both human and mice hematopoietic stem cells (HSCs) carrying DNMT3A mutations into immunodeficient mice with FBM. A significant increase in self-renewal was found when DNMT3AMut-HSCs were exposed to FBM. To better understand the mechanisms of the FBM-CH interaction, we performed single cell RNA-sequencing on HSPCs after FBM exposure in vivo. A 6-10 fold increase in DNMT3AMut-HSCs was observed under FBM conditions in comparison to normal bone marrow. Mutated HSCs from mice exposed to FBM exhibited an activated inflammatory signaling (IL-6 and IFNγ). Cytokine analysis of BM fluid and BM derived adipocytes grown in vitro demonstrated increased IL-6 levels under FBM conditions. Anti-IL-6 neutralizing antibodies significantly reduced the selective advantage of mice derived DNMT3AMut-HSCs exposed to FBM. Overall, paracrine FBM inflammatory signals promote DNMT3A-driven clonal hematopoiesis, which can be inhibited by blocking the IL-6 receptor.

2023-02-19 | E-MTAB-12614 | biostudies-arrayexpress

Inflammatory signals from fatty bone marrow support DNMT3a-driven clonal hematopoiesis (Dnmt3A KI heterozygote subset)

2023-02-19 | E-MTAB-12613 | biostudies-arrayexpress

Aberrant Clonal Hematopoiesis following Lentiviral Vector Transduction of HSPCs in a Rhesus Macaque.

| S-EPMC6554657 | biostudies-literature